It has become apparent that much of the tissue damage in pulmonary diseases, whether the diseases are infectious, pollutant or immunological in origin, relates to the consequences of products released by inflammatory cells, macrophages and granulocytes. Hydrolytic enzymes in inflammatory cells in particular have the capacity to injure lung tissue and cause lung disease. Accordingly, it would be expected that the regulation of the accumulation of inflammatory cells into lung tissue plays a major role in many lung diseases. This accumulation of inflammatory cells in lung tissue is dependent on both the generation and the inactivation of chemotactic factors. The objectives of this proposal are to develop insight on the role of chemotactic factors and the inactivators of chemotactic factors in the induction and regulation of inflammation and injury in lung. Specifically, this study will encompass the role of chemotactic mediators in immune complex-induced and elastase-induced lung injury. To achieve these objectives, efforts will be directed at the following specific aims: 1) To develop quantitative methods to measure the accumulation of leukocytes in lung tissue during injury; 2) To characterize leukotactic factors generated in lung during immune complex and elastase induced lung inflammation and injury; 3) To determine the role of serum complement and neutrophils in elastase induced lung injury; 4) To determine to what extent systematically (intravenous) administered chemotactic factor inactivator (CFI) can modulate lung injury and inflammation induced by immune complexes or elastase; 5) To determine the ability of intrabrochially administered chemotactins to produce inflammatory responses in the lung; 6) To develop a sensitive and reliable biochemical assay for detecting CFI levels in serum; 7) To determine the role of leukocytic products in the generation of chemotactic factors from lung tissue. Understanding the basic mechanisms involved in the generation and inactivation of chemotactins in the lung will provide important insight into the mechanisms of lung disease.